title: Cross talk between O-GlcNAcylation and phosphorylation: roles in signaling, transcription, and chronic disease.
abstract: O-GlcNAcylation is the addition of β-D-N-acetylglucosamine to serine or threonine residues of nuclear and cytoplasmic proteins. O-linked N-acetylglucosamine (O-GlcNAc) was not discovered until the early 1980s and still remains difficult to detect and quantify. Nonetheless, O-GlcNAc is highly abundant and cycles on proteins with a timescale similar to protein phosphorylation. O-GlcNAc occurs in organisms ranging from some bacteria to protozoans and metazoans, including plants and nematodes up the evolutionary tree to man. O-GlcNAcylation is mostly on nuclear proteins, but it occurs in all intracellular compartments, including mitochondria. Recent glycomic analyses have shown that O-GlcNAcylation has surprisingly extensive cross talk with phosphorylation, where it serves as a nutrient/stress sensor to modulate signaling, transcription, and cytoskeletal functions. Abnormal amounts of O-GlcNAcylation underlie the etiology of insulin resistance and glucose toxicity in diabetes, and this type of modification plays a direct role in neurodegenerative disease. Many oncogenic proteins and tumor suppressor proteins are also regulated by O-GlcNAcylation. Current data justify extensive efforts toward a better understanding of this invisible, yet abundant, modification. As tools for the study of O-GlcNAc become more facile and available, exponential growth in this area of research will eventually take place.
authors.affiliation: Departments of Biological Chemistry and Pediatrics, Johns Hopkins University, School of Medicine, Baltimore, Maryland 21205;
authors.forename: Gerald W
authors.initials: GW
authors.lastname: Hart
authors.forename: Chad
authors.initials: C
authors.lastname: Slawson
authors.forename: Genaro
authors.initials: G
authors.lastname: Ramirez-Correa
authors.forename: Olof
authors.initials: O
authors.lastname: Lagerlof
mesh_terms: D000117:Acetylglucosamine / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D002908:Chronic Disease; D003920:Diabetes Mellitus / Q000503:physiopathology; D006031:Glycosylation; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D017351:N-Acetylglucosaminyltransferases / Q000378:metabolism; D009369:Neoplasms / Q000503:physiopathology; D019636:Neurodegenerative Diseases / Q000503:physiopathology; D010766:Phosphorylation; D011487:Protein Conformation; D015398:Signal Transduction / Q000502:physiology*; D014158:Transcription, Genetic
chemical_list: D017351:N-Acetylglucosaminyltransferases; D000117:Acetylglucosamine